This study is designed to investigate those central actions of morphine and related narcotic analgesics which alter autonomic nervous outflow from the brain. The major target organ to be monitored is the intestine. Narcotic drugs will be administered either systemically, intraarterially to specific vascular arcades of the intestine, into the lateral ventricle of the brain, or by microinjection into specific brain regions of anesthetized or, usually, unanesthetized animals. Electrical and contractile activities at several loci on the intestine will be monitored. The effects of the narcotic drugs, given by different routes, on the paterns of contractile and electrical activity will be correlated. Addiction (tolerance and physical dependence) will be produced in animals by systemic morphine administration or by intracerebral injection. Central and peripheral components of tolerance and dependence will be measured and separated. Results of this study are expected to further our understanding of acute and chronic narcotic drug action and also to improve our understanding of central nervous system control of intestinal motility. The undersigned agrees to accept resonsibility for the scientific and technical conduct of the project and for provision of required progress reports if a grant is awarded as the result of this application.